Association between ibrutinib treatment and hypertension

Abstract

Background: Ibrutinib is a tyrosine kinase inhibitor most commonly associated with atrial fibrillation. However, additional cardiotoxicities have been identified, including accelerated hypertension. The incidence and risk factors of new or worsening hypertension following ibrutinib treatment are not as well known.

Methods: We conducted a retrospective study of 144 patients diagnosed with B cell malignancies treated with ibrutinib (n=93) versus conventional chemoimmunotherapy (n=51) and evaluated their effects on blood pressure at 1, 2, 3 and 6 months after treatment initiation. Descriptive statistics were used to compare baseline characteristics for each treatment group. Fisher's exact test was used to identify covariates significantly associated with the development of hypertension. Repeated measures analyses were conducted to analyse longitudinal blood pressure changes.

Results: Both treatments had similar prevalence of baseline hypertension at 63.4% and 66.7%, respectively. There were no differences between treatments by age, sex and baseline cardiac comorbidities. Both systolic and diastolic blood pressure significantly increased over time with ibrutinib compared with baseline, whereas conventional chemoimmunotherapy was not associated with significant changes in blood pressure. Baseline hypertensive status did not affect the degree of blood pressure change over time. A significant increase in systolic blood pressure (defined as more than 10 mm Hg) was noted for ibrutinib (36.6%) compared with conventional chemoimmunotherapy (7.9%) at 1 month after treatment initiation. Despite being hypertensive at follow-up, 61.2% of patients who were treated with ibrutinib did not receive adequate blood pressure management (increase or addition of blood pressure medications). Within the ibrutinib group, of patients who developed more than 20 mm Hg increase in systolic blood pressure, only 52.9% had hypertension management changes.

Conclusions: Ibrutinib is associated with the development of hypertension and worsening of blood pressure. Cardiologists and oncologists must be aware of this cardiotoxicity to allow timely management of blood pressure elevations.

Keywords: drug monitoring; health care; hypertension; outcome assessment.

Figure 1

Changes in blood pressure over time based on treatment group. (A) Changes in systolic blood pressure over time based on treatment regimen. Ibrutinib treatment causes significant increase in systolic blood pressure over time compared with baseline. (B) Changes in diastolic blood pressure over time based on treatment regimen. In a repeated measure post-hoc Bonferroni test, there was statistically significant increase in blood pressure at 1 month and at 2–6 months summary data when compared with baseline (p<0.001) in the ibrutinib group.

Figure 2

Box plot for changes in blood pressure from baseline to 1 month by treatment and baseline hypertension status. Systolic (A) and diastolic (B) blood pressure changes from baseline and 1 month were not different between hypertension (red bar) and normotension (blue bar) in both ibrutinib and conventional chemoimmunotherapy groups. Changes in systolic and diastolic blood pressure were significantly different overall for ibrutinib versus conventional chemoimmunotherapy (p<0.001) in the ibrutinib group. Δ, change in blood pressure; DBP, diastolic blood pressure; HTN, hypertension; NS, not statistically significant; SBP, systolic blood pressure.